JP2009069006A - Cantilever sensor, material detecting system using the same, and material testing system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a cantilever sensor having high measuring accuracy and reduced in size and cost. <P>SOLUTION: This sensor includes a cantilever fixed to a support part at its one end and having a flow passage formed therein, a piezoelectric element constituted by a piezoelectric body and electrode parts formed on the both sides of the piezoelectric body and disposed at least on one surface of the cantilever, a driving part applying voltage to the electrode parts of the piezoelectric element to vibrate the cantilever, a detecting part detecting vibration of the cantilever from expansion and contraction of the piezoelectric element and a liquid supplying means letting a liquid flow through the flow passage in the cantilever. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a cantilever type sensor, a substance detection system using the sensor, and a substance inspection method.

In recent years, mainly in the field of biotechnology, the need to detect fine substances such as proteins, cells, viruses, and bacteria has increased, and fine substance detection apparatuses and methods have been developed.
Optical methods such as SPR (Surface Plasmon Resonance) measurement using surface plasmon resonance have been put to practical use as high-sensitivity detection methods, but cantilevers that detect fine substances from the amount of deflection and frequency of the cantilever. A detection device using a mold sensor has also been proposed (Patent Document 1 and Patent Document 2).

For example, Patent Document 1 describes a sensor system having a measurement cantilever in which a coating sensitive to a target material is applied to one surface and a reference cantilever in which a coating not sensitive to the target material is applied to the surface. .
In this sensor system, the reference liquid is exposed in the reference step and both cantilevers in the detection step are exposed to the reference liquid having the target substance, so that the deflection between the measurement cantilever and the reference cantilever between the reference step and the detection step is reduced. The difference is detected. In addition, a method using an optical sensor is described as a method for detecting deflection.

Patent Document 2 describes a cantilever sensor type analysis system having a cantilever in which a driving film and an electric pad are laminated on an upper surface and a molecule recognition layer formed of a substance that reacts with a substance to be measured is laminated on a lower surface. ing.
In this system, after the reactant is fixed to the molecular recognition layer of the cantilever, the cantilever is vibrated by the driving film, and the frequency of the cantilever is detected by the electric pad.
By comparing the sensed resonance frequency with the resonance frequency measured in a state where the reactant is not fixed to the molecule recognition layer, the amount of the reactant attached to the molecule recognition layer is detected.

  Further, Non-Patent Document 1 describes a cantilever type sensor in which a flow path is provided in a cantilever, and a liquid to be measured or a liquid having a measurement target is flowed into the flow path to measure the mass of the measurement target. Yes.

JP-T-2004-506872 JP 2005-156526 A Nature vol446 p1066-1069 (2007)

Here, as in the systems described in Patent Document 1 and Patent Document 2, the method of adsorbing a substance on one surface of the cantilever is to place the cantilever in the fluid, so that the mechanical quality factor Q of the cantilever decreases, There is a problem that sensitivity decreases.
Moreover, although the measurement object is selectively adsorbed by the antigen-antibody reaction, non-specific adsorption occurs, so that the measurement accuracy cannot be increased.

On the other hand, like the cantilever described in Non-Patent Document 1, by forming a flow path inside, it can be vibrated in the air, and the mechanical quality factor Q is made higher than when vibrating in a solution. be able to. Moreover, since measurement can be performed without adsorbing the measurement target, measurement can be performed without causing non-specific adsorption.
However, the cantilever described in Non-Patent Document 1 has a problem that the apparatus becomes large because a drive mechanism that vibrates the cantilever by an electrostatic method and a detection unit that detects deflection by an optical sensor are used.

  An object of the present invention is to provide a cantilever-type sensor, a substance detection system and a substance detection method using the same, which solve the above-mentioned problems based on the prior art, have high measurement accuracy, are small and low in cost.

  In order to solve the above problems, a first embodiment of the present invention is a cantilever type sensor that detects a measurement object contained in a liquid, and has one end fixed to a support portion and a flow path formed therein. A cantilever, a piezoelectric body, and a piezoelectric element formed on both surfaces of the piezoelectric body, a piezoelectric element disposed on at least one surface of the cantilever, and a voltage is applied to the electrode section of the piezoelectric element, and the cantilever A cantilever type sensor having a drive unit that vibrates, a detection unit that detects vibration of the cantilever from expansion and contraction of the piezoelectric element, and a liquid supply unit that causes liquid to flow through the flow path of the cantilever.

Here, the piezoelectric body is preferably a composition of perovskite crystal containing Pb from the viewpoint of enhancing piezoelectric characteristics. The piezoelectric body is preferably a composition of perovskite crystals not containing Pb from the viewpoint of environmental protection. Here, the composition containing no Pb is a composition having a Pb content of 0.1 w% or less.
Moreover, it is preferable that only one end of the cantilever is fixed to the support portion. Moreover, it is also preferable that both ends of the cantilever are fixed to the support portion.

  In order to solve the above-described problem, a second embodiment of the present invention includes a cantilever sensor according to any one of the above, a frequency calculation unit that calculates a resonance frequency of the cantilever from a value detected by a detection unit, The resonance frequency calculated by the calculation unit is compared with the resonance frequency of the cantilever when a liquid that does not contain the measurement object flows through the flow path, and the measurement object in the flow path is detected from the comparison result. A substance detection system having a detection unit is provided.

Here, it is preferable that the detection unit detects the mass of the measurement target from the comparison result.
Moreover, it is also preferable that the detection unit detects the presence or absence of the substance to be measured from the comparison result.

  In order to solve the above problems, a third embodiment of the present invention is a substance detection method for detecting a measurement target in a liquid, wherein a piezoelectric element is disposed on at least one surface, and a flow path is formed inside. A liquid is caused to flow through the flow path of the cantilever, a voltage is applied to the piezoelectric element, and the piezoelectric element is expanded and contracted to vibrate the cantilever in the state where the liquid is flowed, and the vibration of the cantilever is And detecting the resonance frequency of the cantilever in a state in which the liquid is flowed from the detected vibration, and the resonance frequency of the cantilever in a state in which a liquid not containing a measurement target is flowed in the flow path The present invention provides a substance detection method for comparing a frequency and detecting a measurement object from the comparison result.

  Here, it is preferable that the substance detection method detects the mass of the measurement target from the comparison result.

According to the present invention, since detection can be performed by flowing a liquid through a flow path formed in the cantilever, the cantilever can be vibrated in the air, and the measurement object is allowed to flow in the flow path without being adsorbed. Since it can be detected, it can be detected without causing non-specific adsorption. Thereby, measurement accuracy can be made high.
Further, since the excitation of the cantilever and the detection of the vibration of the cantilever can be performed by the piezoelectric element, the device configuration can be simplified and the device can be miniaturized.
Further, since the apparatus configuration can be simplified and reduced in size, it can be easily arrayed.

  A cantilever type sensor, a substance detection system using the cantilever sensor, and a substance detection method according to the present invention will be described in detail based on embodiments shown in the accompanying drawings.

  1 is a schematic diagram showing a schematic configuration of a substance detection system of the present invention using the cantilever type sensor of the present invention, and FIG. 2 is a schematic configuration of a cantilever and a support portion of a main body portion of the cantilever type sensor shown in FIG. 3A is a top cross-sectional view of the main body of the cantilever type sensor shown in FIG. 1, and FIG. 3B is a side view of the main body of the cantilever type sensor shown in FIG. It is sectional drawing.

As shown in FIG. 1, the substance detection system 10 flows a liquid containing a measurement object into the cantilever, and the cantilever type sensor 12 whose cantilever resonance frequency changes depending on the measurement object flowing inside, and the resonance of the cantilever type sensor 12. A frequency calculation unit 14 that calculates the frequency and a mass calculation unit 16 that calculates the mass of the measurement target from the resonance frequency calculated by the frequency calculation unit 14 are included.
Here, the measurement target is a fine substance, and examples thereof include proteins, cells, viruses, bacteria, nanoparticles, beads, and the like.
Moreover, although the liquid which contains a measuring object is not specifically limited, Water, alcohol, etc. are illustrated.

First, the cantilever type sensor 12 will be described.
The cantilever type sensor 12 includes a main body 20, a signal source 22, a mixer 24, a duplexer 26, a detector 28, and a liquid supply / recovery unit 30.

  As shown in FIGS. 2, 3 (A) and 3 (B), the main body 20 includes a cantilever 32, a support 34 that supports one end of the cantilever 32, and a piezoelectric element 36 disposed on the upper surface of the cantilever 32. Have

The cantilever (cantilever beam) 32 is a beam having one end supported by a support portion 34. The support portion 34 is a base that supports one end of the cantilever 32, and is formed integrally with the cantilever 32.
The cantilever 32 and the support part 34 have a flow path 38 formed therein.
As shown in FIG. 2, the flow path 38 passes from the support portion 34 through the proximal end of the cantilever 32, extends to the distal end portion of the cantilever 32, is folded back at the distal end portion of the cantilever 32, and extends from the proximal end portion of the cantilever 32. It is formed so as to pass through the support portion 34.
That is, the part formed in the cantilever 32 of the flow path 38 is formed in a U-shape in which the tip part is a folded part. Further, in the portion formed in the support portion 34 of the flow path 38, two flow paths connected to the two flow paths on the proximal end side of the cantilever 32 are formed. Further, the two flow paths 38 of the support part 34 are respectively connected to a liquid supply / recovery part 30 described later.

  The piezoelectric element 36 is disposed on the upper surface of the cantilever 32 and includes a lower electrode 40, a piezoelectric body 42, an upper electrode 44, a protective layer 46, and extraction electrodes 48 and 50.

The lower electrode 40 is a plate-like electrode disposed on the upper surface of the cantilever 32. The lower electrode 40 is connected to a mixer 24 described later via an extraction electrode 48.
Here, the lower electrode 40 can be made of various materials, for example, a metal such as Au, Pt and Ir, a metal oxide such as IrO ₂ , RuO ₂ , LaNiO ₃ and SrRuO ₃ and combinations thereof. Can be produced.

The piezoelectric body 42 is a member formed on the lower electrode 40 and having a certain thickness in a direction from the upper electrode 44 toward the lower electrode 40 (vertical direction in FIG. 3B). The piezoelectric body 42 is formed of a material that expands and contracts by changing the applied voltage, and outputs a predetermined voltage by expanding and contracting. In this embodiment, Pb _{x By y} O _z is mainly used. It is formed as a component. Here, x, y, z are arbitrary real numbers, B is an element of the B site, Ti, Zr, V, Nb, Ta, Cr, Mo, W, Mn, Sc, Co, Cu, It is composed of at least one of In, Sn, Ga, Zn, Cd, Fe, and Ni. In addition, the piezoelectric body is standard when x = y = 1 and z = 3, and x and y can be changed to various values within a range where a perovskite structure can be taken. In the case where Pb _x B _y O _z is the main component, the piezoelectric characteristics such as the piezoelectric coefficient can be enhanced by using the perovskite structure. Thereby, it can be greatly expanded and contracted by applying a low voltage.

  Here, the piezoelectric body 42 is preferably composed mainly of lead zirconate titanate (PZT) having Zr and Ti as B-site elements. By using PZT as the main component, the piezoelectric characteristics can be enhanced and the cost can be made relatively low.

The piezoelectric body is not limited to lead zirconate titanate (PZT), but lead such as lead titanate, lead zirconate, lead lanthanum titanate, lead lanthanum zirconate titanate, lead zirconium niobate, zirconium titanate titanate, etc. Containing compounds can be used.
In the present embodiment, Pb _x B _y O _z is the main component, but the so-called A site does not contain lead, bismuth potassium titanate, sodium niobate, potassium niobate, lithium niobate, bismuth ferrite. In addition, solid solutions thereof can also be used.
Also in the case of forming a piezoelectric body with the above composition, it is preferable to have a perovskite structure. By making the piezoelectric body a perovskite structure of the above composition, the piezoelectric characteristics can be enhanced. In addition, by using a piezoelectric material having a perovskite structure composition containing Pb, the piezoelectric characteristics can be further improved. As described above, by using a piezoelectric material having a perovskite structure composition that does not contain Pb. , Environmental protection can be achieved. Here, “does not contain Pb” means a composition having a Pb content of 0.1 w% or less in the composition, and the above-described materials are exemplified.
In addition, as described above, it is preferable to use a piezoelectric body having a perovskite structure, but the piezoelectric body is not limited thereto, and is made of zinc oxide (ZnO), aluminum nitride (AlN), tantalum pentoxide (Ta ₂ O ₅ ), or the like. Can also be used.

Here, the piezoelectric body 42 can be produced by various methods such as bulk sintering, screen printing, and spin coating, but is preferably produced by a vapor phase growth method. Specifically, sputtering method, ion beam sputtering method, ion plating method, PLD (Pulsed Laser Deposition) method, CVD using vapor phase growth method using plasma, vapor phase growth method using light, heat, etc. It is preferable to produce by various vapor phase growth methods such as (Chemical Vapor Deposition) method.
By producing by a vapor phase growth method, it is possible to produce a piezoelectric body without performing an annealing treatment and the like, and lead can be prevented from being lost, so that a uniform piezoelectric body can be formed.

The upper electrode 44 is a plate-like electrode, and is disposed on the surface opposite to the surface on which the lower electrode 40 of the piezoelectric body 42 is disposed. That is, the upper electrode 44 and the lower electrode 40 are disposed so as to sandwich the piezoelectric body 42. The upper electrode 44 is connected to a mixer as will be described later via an extraction electrode 50.
The upper electrode 44 can be made of various materials, for example, metals such as Au, Pt and Ir, metal oxides such as IrO ₂ , RuO ₂ , LaNiO ₃ and SrRuO ₃ , Al, Ta, Cr and the like. It can be made of an electrode material generally used in a semiconductor process, such as Cu, or a combination thereof.
Further, the upper electrode 44 may have a multilayer structure in which an adhesion layer and an electrode layer are laminated in order to improve adhesion with the piezoelectric body.

Next, the protective layer 46 is formed of an insulating material such as SiO ₂ and covers exposed portions of the lower electrode 40, the piezoelectric body 42, and the upper electrode 44 except for the extraction electrodes 48 and 50.
By providing the protective layer 46, the exposed portions of the lower electrode 40, the piezoelectric body 42, and the upper electrode 44 are eliminated, and it is possible to prevent the occurrence of discharge, leakage, and the like.

The main body 20 is basically configured as described above.
Next, the signal source 22 is a power source for applying a voltage, and is connected to the lower electrode 40 and the upper electrode 44 of the piezoelectric element 36 via the mixer 24.
The mixer 24 is connected to the piezoelectric element 36, the signal source 22, and the duplexer 26. The mixer 24 supplies the voltage output from the signal source 22 to the piezoelectric element 36, and further supplies the voltage output from the piezoelectric element 36 to the duplexer 26.

The duplexer 26 receives the voltage generated by the deformation of the piezoelectric body 42 of the piezoelectric element 36 due to the vibration of the cantilever 32 from the mixer 24 and divides the voltage for each frequency.
The detector 28 calculates the intensity of each frequency from the output of each frequency divided by the duplexer 26.
Further, the liquid supply / recovery unit 30 is connected to the respective ends of the two flow channels 38 of the support unit 34, supplies the liquid to the flow channel 38, and collects the liquid flowing through the flow channel 38. To do.
Here, the liquid supply / recovery unit 30 supplies the liquid containing the measurement target and the liquid not containing the measurement target as the liquid. As will be described later, the liquid not containing the measurement target is used to calculate a reference for detecting the mass of the measurement target.
The cantilever type sensor 12 is basically configured as described above.

The frequency calculation unit 14 detects the resonance frequency of the cantilever 32 based on the value detected by the detector 28.
The mass calculation unit 16 compares the resonance frequency of the cantilever 32 with the resonance frequency of the cantilever 32 in a state where a liquid that does not contain the measurement object flows in the flow path 38 detected in advance, and calculates the mass of the measurement object from the difference. calculate.

The substance detection method of the present invention using the substance detection system 10 will be described.
4 and 5 are flowcharts showing examples of the substance detection method of the present invention.

The substance detection system 10 detects the resonance frequency of the cantilever when a liquid that does not contain the substance to be measured flows through the flow path before detecting the substance to be measured.
First, the liquid that does not contain the measurement target is caused to flow from the liquid supply / recovery unit 30 to the flow path 38, and the liquid that does not contain the measurement target flows into the flow path 38 of the cantilever 32 (step S12).

  Next, the cantilever 32 in which the liquid is flowing is vibrated by the piezoelectric element 36 (step S14). Specifically, a pulse wave having a predetermined potential is generated by the signal source 22 and applied to the upper electrode 44 of the piezoelectric element 36 via the mixer 24. A constant voltage is applied to the lower electrode 40. Thus, when a voltage is applied to the lower electrode 40 and the upper electrode 44, a potential difference is generated in the piezoelectric body 42, and the piezoelectric body 42 expands and contracts. A force is applied to the cantilever 32 by the expansion and contraction of the piezoelectric body 42, and the cantilever 32 is displaced by a certain amount. Thereafter, the cantilever 32 returns to the position before the displacement while being damped and oscillated.

The resonance frequency of the cantilever 32 is calculated from the vibration of the cantilever 32 (step S16). Specifically, the calculation is performed as follows.
The cantilever 32 vibrates when force is applied from the piezoelectric body 42. As the cantilever 32 vibrates, the piezoelectric body 42 disposed on the upper surface of the cantilever 32 also expands and contracts. When the piezoelectric body 42 expands and contracts (that is, deforms), a voltage is generated.
The voltage generated in the piezoelectric body 42 is detected by the lower electrode 40 and the upper electrode 44 and sent to the duplexer 26 via the mixer 24. The demultiplexer 26 demultiplexes the voltage change sent from the mixer 24 into frequency components and sends it to the detector 28. The detection unit 30 detects each demultiplexed frequency component and sends a detection result to the frequency calculation unit 14.
The frequency calculation unit 14 calculates the resonance frequency of the cantilever 32 from the frequency component of the vibration of the cantilever 32 detected by the detector 30.
As described above, the resonance frequency of the cantilever 32 in which the liquid not containing the measurement target flows through the flow path 38 is calculated.

Next, the mass of the measurement target is calculated.
First, the liquid containing the measurement target is caused to flow from the liquid supply / recovery unit 30 to the flow path 38, so that the liquid containing the measurement target is flowing into the flow path 38 of the cantilever 32 (step S22).

  Next, the cantilever 32 in which the liquid is flowing is vibrated by the piezoelectric element 36 (step S24). Specifically, as in step S <b> 14, a predetermined voltage is applied to the upper electrode 44 of the piezoelectric element 36 to expand and contract the piezoelectric body 44, thereby vibrating the cantilever 32.

Next, the resonance frequency of the cantilever 32 is calculated from the vibration of the cantilever 32 (step S26). Specifically, as in step S16 described above, the vibration of the cantilever 32 is detected by the piezoelectric element 36, and the frequency component is detected by the mixer 24, the demultiplexer 26, and the detector 28. Thereafter, the frequency calculation unit 14 calculates the resonance frequency of the cantilever 32 from the frequency component of the vibration of the cantilever 32 detected by the detector 30.
As described above, the resonance frequency of the cantilever 32 in which the liquid containing the measurement target flows through the flow path 38 is calculated.

Next, the resonance frequency of the cantilever 32 in which the liquid containing the measurement target detected in step S26 flows through the flow path 38, and the resonance frequency of the cantilever 32 in which the liquid not containing the measurement target detected in step S16 flows in the flow path 38. Is calculated (step S28).
Specifically, the mass calculation unit 16 compares the resonance frequency detected in step S26 with the resonance frequency detected in step S16, and calculates the difference between the two resonance frequencies.

Next, the mass to be measured is detected from the difference between the calculated resonance frequencies (step S30).
Specifically, the mass calculation unit 16 calculates the mass of the measurement target contained in the liquid in the flow path 38 of the cantilever 32 from the difference between the resonance frequencies calculated in step S28.
As described above, the mass of the measurement target is calculated.

In this way, by providing a channel in the cantilever, flowing a liquid including the measurement target in the channel and calculating the mass of the measurement target, the cantilever can be vibrated in the air. Thereby, mechanical quality factor Q can be made higher than the case where mass is detected by arranging a cantilever in a liquid and vibrating it in a state where a measurement object is attached to the surface of the cantilever.
In addition, since there is no need to attach the measurement target to the cantilever, non-specific adsorption can be prevented, and fine substances that could not be attached to the cantilever can be detected. Can be detected.
In addition, it is possible to remove the fine substances remaining by simple cleaning in the flow path, so that the cantilever can be used multiple times with simple cleaning, and the possibility that the measurement object remains at the previous detection can be reduced. Measurement accuracy can be increased.

  Furthermore, by vibrating the cantilever with a piezoelectric element and further detecting the vibration of the cantilever, that is, by performing both excitation and vibration detection with the piezoelectric element, the device can be made small and inexpensive, The apparatus configuration can be simplified. Moreover, since the apparatus can be made inexpensive, it can be used up.

Here, in the said embodiment, although the resonant frequency of the liquid which does not contain a measuring object previously was measured, this invention is not limited to this. Hereinafter, another example of the measurement method will be described with reference to FIG.
FIG. 6 is a flowchart for explaining another example of the substance detection method of the present invention. Here, the fluid containing the measurement target of the present embodiment is a liquid with a small content of the measurement target, and the measurement target may or may not flow in the flow path 38 of the cantilever 32.

  First, the liquid containing the measurement target is caused to flow from the liquid supply / recovery unit 30 to the flow path 38, so that the fluid containing the measurement target is flowing to the flow path 38 of the cantilever 32 (step S22).

  Next, the cantilever 32 in which the liquid is flowing is vibrated by the piezoelectric element 36 (step S24). Specifically, as in step S <b> 14, a predetermined voltage is applied to the upper electrode 44 of the piezoelectric element 36 to expand and contract the piezoelectric body 44, thereby vibrating the cantilever 32.

Next, the resonance frequency of the cantilever 32 is calculated from the vibration of the cantilever 32 (step S26). Specifically, as in step S16 described above, the vibration of the cantilever 32 is detected by the piezoelectric element 36, and the frequency component is detected by the mixer 24, the demultiplexer 26, and the detector 28. Thereafter, the frequency calculation unit 14 calculates the resonance frequency of the cantilever 32 from the frequency component of the vibration of the cantilever 32 detected by the detector 30.
As described above, the resonance frequency of the cantilever 32 in which the liquid containing the measurement target flows through the flow path 38 is calculated.

Next, it is determined whether a predetermined time (that is, a preset arbitrary time) has elapsed since the start of measurement (step S40).
If the predetermined time has not elapsed, that is, before the predetermined time has elapsed, the process returns to step S24, the cantilever 32 is vibrated again, and the resonance frequency of the cantilever 32 in which the liquid containing the measurement object flows through the flow path 38 is calculated. That is, the detection of the resonance frequency is repeated until a predetermined time has elapsed.

On the other hand, if the predetermined time has passed in step S40, the process proceeds to step S42.
When a predetermined time has elapsed from the start of measurement, the resonance frequency of the cantilever 32 in which the liquid containing the measurement target is detected a plurality of times by repeating step S24 and step S26 until the predetermined time elapses, and so on. A portion having a resonance frequency different from that of the portion (hereinafter also referred to as “change portion”) is detected (step S42).
Specifically, the resonance frequency detected a plurality of times changes depending on whether or not the measurement object is flowing in the flow path 38. Therefore, the resonance frequency detected a plurality of times is caused to flow by the resonance frequency. The resonance frequency is detected when the measurement target is flowing in the path and the resonance frequency is detected when the measurement target is not flowing in the flow path. And the resonance frequency detected in the state in which the measuring object is flowing in the flow path is detected as the resonance frequency of the changed portion.

Next, the mass to be measured is detected from the difference between the detected resonance frequency of the changed portion and the resonance frequency of the other portion (step S44).
Specifically, the difference between the resonance frequency detected in a state where the measurement object flows in the flow path and the resonance frequency of the cantilever 32 in which the liquid not containing the measurement object flows through the flow path 38 is calculated, and the resonance frequency From the difference, the mass of the measurement target contained in the liquid in the flow path 38 of the cantilever 32 is calculated.
As described above, the mass of the measurement target may be calculated.

In this way, the mass of the measurement target can be detected by detecting the resonance frequency a plurality of times while flowing the liquid containing the measurement target and calculating the difference between the resonance frequencies.
In this way, even when only one liquid is flowed, the resonance frequency can be detected a plurality of times, and the mass of the measurement object can be detected from the difference. In addition, when the resonance frequency is detected a plurality of times and the mass of the measurement target is detected based on the difference, it is preferable to use a liquid with a small content of the measurement target as the liquid. Specifically, the liquid in which the measurement object is flowing or not flowing in the flow path in the cantilever, that is, the liquid in which the number of measurement objects per volume of the flow path in the cantilever is less than one. It is preferable that

In addition, the measurement target is not limited to whether or not the flow of the cantilever is flowing, the resonance frequency is detected a plurality of times, and one measurement target is flowing in the cantilever, and two are flowing, You may divide into the case where three are flowing, and may detect the mass of a measuring object by each difference.
Here, in this embodiment, the resonance frequency is detected once by one excitation. However, the present invention is not limited to this, and the timing of the excitation and the detection of the resonance frequency may be set to an arbitrary timing. .
In the above embodiment, the resonance frequency is repeatedly detected until the predetermined time is reached. However, the number of times the resonance frequency is detected and the criterion for determining the end of the detection are not limited to this, and the resonance frequency is detected a predetermined number of times. Alternatively, the resonance frequency may be repeatedly detected until the liquid is completely flowed, or the resonance frequency may be repeatedly detected until an operator gives an instruction.

Here, in the present embodiment, the number of cantilevers is one. However, as shown in FIG. 7, a configuration in which a plurality of cantilevers 32 are arranged on a main body 70 and a support 72 is also possible.
By detecting a measurement object using a plurality of cantilevers, it can be detected more accurately. It is also possible to detect changes in the substance to be measured by gradually changing the experimental conditions for each cantilever.
Further, even when a plurality of cantilevers are arranged, it is possible to reduce the size by providing excitation and vibration detection by providing one piezoelectric element for each cantilever. As a result, the cantilevers can be arranged at high density, and the array can be easily arranged.

Moreover, when arranging a plurality of cantilevers, it is preferable to connect the flow paths of adjacent cantilevers. That is, it is preferable to connect the flow path on the outflow side of one cantilever and the flow path on the inflow side of the other cantilever.
By connecting the flow paths of adjacent cantilevers, the same measurement object can be measured multiple times. Thereby, it can detect still more correctly.
The same measurement object can also be detected under different conditions (for example, conditions with different liquid properties, different temperature conditions, etc.).

Moreover, although mass was detected in this embodiment, this invention is not limited to this, You may detect the presence or absence of a measuring object. In this case, mass detection by the mass detection unit is not performed, and it is only necessary to detect whether or not the measurement target is in the flow path of the cantilever by comparing the resonance frequencies.
In this case, as a liquid, a liquid that is unknown whether or not it contains a measurement target is caused to flow through the flow path of the cantilever, and the resonance frequency of the cantilever when the liquid is supplied and a liquid that does not contain the measurement target. The resonance frequency of the cantilever when flowing is compared, and when the resonance frequency changes, something other than liquid is mixed.
In this way, it can also be used to detect the presence or absence of a measurement target, and since the measurement accuracy is particularly high, the presence or absence of a finer substance can also be detected.

  In the present embodiment, the cantilever is displaced, the frequency of the damped vibration until it returns to the original position is detected, and the resonance frequency of the cantilever is detected, but the present invention is not limited to this, and the cantilever by the piezoelectric element is detected. The excitation frequency may be gradually changed, the vibration of the cantilever at each excitation frequency may be detected by a piezoelectric element, and the resonating frequency may be detected. In this case, the excitation frequency can be changed by changing the pulse width of the voltage applied to the upper electrode of the piezoelectric element by the signal source.

The cantilever type sensor is preferably provided with a container for sealing the cantilever, the inside of the container is decompressed, and the cantilever is disposed in an atmosphere lower than atmospheric pressure, and the inside of the container is more preferably in a vacuum state.
By vibrating the cantilever at a low pressure, that is, in a thinner air state, the mechanical quality factor Q can be increased, the measurement accuracy can be further increased, and the cantilever is measured by vibrating in a vacuum. The accuracy can be further increased.

  Further, the shape of the flow path formed inside the cantilever is not particularly limited, and the flow path may meander in the cantilever. Further, the two flow paths that are folded back may be overlapped in the thickness direction of the cantilever.

  Further, the arrangement position of the piezoelectric element is not limited to the upper surface of the cantilever, and may be arranged on the lower surface. Further, since the amplitude of the cantilever can be increased and the resonance frequency can be detected by the vibration of the primary mode, the piezoelectric element is preferably disposed on the surface having the largest surface area of the cantilever, that is, the upper surface or the lower surface in this embodiment. It may be arranged on the side.

  Further, the detection timing of the resonance frequency of the cantilever when the liquid not containing the measurement target flows in the flow path is not particularly limited, and may be performed every time before detecting the measurement target or every predetermined number of times. Good. When the same liquid is used as the liquid, the resonance frequency detected when first used can be used.

Next, the manufacturing method of the cantilever type sensor of the present invention will be described.
8A to 8K are process diagrams showing an example of the manufacturing process of the main body of the cantilever type sensor of the present invention.

First, an SOI substrate 100 in which a Si layer 102, a SiO ₂ layer 104, and a Si layer 106 were stacked was used as a substrate (see FIG. 8A).
The Si layer 106 of the SOI substrate 100 is dry-etched to form a channel 108 in the Si layer 106 (see FIG. 8B).
Next, the SOI substrate 110 in which the Si layer 112 and the SiO ₂ layer 114 are stacked is attached to the surface of the Si layer 106 of the SOI substrate 100 (see FIG. 8C). Here, the SOI substrate 100 and the SOI substrate 110 are attached so that the Si layer 106 and the Si layer 112 are bonded. Further, the attaching method is not particularly limited, and various methods such as adhesion with an adhesive can be used.

Next, the SiO ₂ layer 114 of the SOI substrate 110 is etched and polished to form a SiO ₂ layer 114 ′ (see FIG. 8D).
Next, the lower electrode 116 is formed over the SiO ₂ layer 114 ′ of the SOI substrate 110 (see FIG. 8E). Specifically, the lower electrode 116 is formed by providing a metal film such as Pt or Ti on the SiO ₂ layer 114 ′ by sputtering or bonding.
Next, the piezoelectric body 118 is formed over the lower electrode 116 (see FIG. 8F).
As a specific example, a PZT fired body is used as a target, and a PZT piezoelectric body 118 is formed on the lower electrode 116 by sputtering. Alternatively, the piezoelectric body 118 may be attached to the lower electrode 116 without being limited to sputtering.
Next, the upper electrode 120 is formed over the piezoelectric body 118 (see FIG. 8G). Specifically, the upper electrode 120 is formed by providing a metal film such as Pt on the piezoelectric body 118 by sputtering or pasting.

Next, the SiO ₂ layer 114 ′, the Si layer 112, the Si layer 106, and the SiO ₂ layer 104 are sequentially etched to form the groove 122. Here, the groove portion 122 is formed along three sides (two sides parallel to the longitudinal direction and one side parallel to the short direction) of the lower electrode 116, and includes a portion serving as a cantilever and a portion serving as a support portion. To separate. Further, one side where the groove portion 122 is not formed is a connection portion between the cantilever and the support portion.

Next, the protective layer 124 is formed on the region where the lower electrode 116, the piezoelectric body 118, and the upper electrode 120 are formed and on the periphery thereof, that is, on the support portion on the side where the cantilever is connected to the cantilever. (See FIG. 8I). Specifically, a protective layer 124 is formed by forming a SiO ₂ film by sputtering, plasma CVD, or the like on a region where the lower electrode 116, the piezoelectric body 118, and the upper electrode 120 are formed and on the upper surface in the vicinity thereof. . This protective layer 124 covers and exposes the exposed portions of the lower electrode 116, the piezoelectric body 118, and the upper electrode 120.

Next, openings are formed in part of the upper surface of the lower electrode 116 of the protective layer 124 and part of the upper surface of the upper electrode 120. After that, the extraction electrode 126 is formed in the opening formed in the upper surface of the lower electrode 116, and the extraction electrode 128 is formed in the opening formed in a part of the upper portion of the upper electrode 120 (see FIG. 8J).
Here, the method of forming the opening in the protective layer 124 is exemplified by etching, and the method of forming the extraction electrode 126 and the extraction electrode 128 is exemplified by sputtering. Moreover, Au is illustrated as a metal used for an extraction electrode.
In this manner, a piezoelectric element composed of the lower electrode 116, the piezoelectric body 118, the upper electrode 120, the protective layer 124, and the extraction electrodes 126 and 128 is formed.

Thereafter, the Si layer 102 of the SOI substrate 100 is dry-etched from the lower surface side (the surface opposite to the SiO ₂ layer 104) to form an opening 130 (see FIG. 8K).
By forming the opening 130 in the Si layer 102, the Si layer 102, the support portion formed thereon, the other portions of the Si layers 106 and 112, and the SiO ₂ layers 104 and 114 ′ are formed. The cantilever formed with 108 is separated except for the joint.
As described above, a main body having a cantilever, a support portion, and a piezoelectric body can be manufactured.
Thereafter, a cantilever type sensor can be manufactured by connecting a liquid supply / recovery unit, a mixer, and the like to the main body.

  Here, the cantilever type sensor, the substance detection system and the substance detection method using the same of the present invention can be used for analysis and detection of fine substances, and can be used for flow cytometry, drug discovery screening, and the like.

  As described above, the cantilever type sensor, the substance detection system and the substance detection method using the cantilever type sensor according to the present invention have been described in detail. However, the present invention is not limited to the above embodiment and does not depart from the gist of the present invention. Various improvements and changes may be made within the scope.

  For example, in the present embodiment, only one end of the cantilever is fixed to the support portion, but both ends of the cantilever may be fixed, that is, a configuration in which both ends of the plate-like member are fixed to the support body may be adopted. By fixing the cantilever of the cantilever type sensor (or beam type sensor) at both ends, it is not cantilevered and the amplitude is reduced, but the durability can be increased. Further, the flow path may be a straight line without a folded portion, that is, a flow path extending from one connection portion between the plate-like member and the support portion to the other connection portion. By making the flow path linear in this way, it is possible to prevent the target substance from being clogged by the flow path in the cantilever, and the measurement accuracy when used multiple times can be increased.

It is a schematic diagram which shows schematic structure of the substance detection system of this invention using the cantilever type | mold sensor of this invention. It is a perspective view which shows schematic structure of the cantilever and support part of the main-body part of the cantilever type sensor shown in FIG. (A) is a top sectional view of the main body of the cantilever type sensor used in the substance detection system shown in FIG. 1, and (B) is a side sectional view of the main body of the cantilever type sensor used in the substance detection system shown in FIG. FIG. It is a flowchart for demonstrating an example of the substance detection method of this invention. It is a flowchart for demonstrating an example of the substance detection method of this invention. It is a flowchart for demonstrating another example of the substance detection method of this invention. It is a top view which shows schematic structure of another example of the cantilever type | mold sensor of this invention. (A)-(K) are process drawings which show the production method of the main-body part of the cantilever type | mold sensor of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Material detection system 12 Cantilever type sensor 14 Frequency calculation part 16 Mass calculation part 20, 70 Main-body part 22 Signal source (transmitter)
24 Mixer
26 Demultiplexer (frequency electric heater)
28 Detector 30 Liquid supply / recovery part 32, 132 Cantilever 34, 72, 134 Support part 36 Piezoelectric element 38, 108 Flow path 40, 116 Lower electrode 42, 118 Piezoelectric element 44, 120 Upper electrode 46, 124 Protective layer 48, 50 126, 128 Extraction electrode 100, 110 SOI substrate 102, 106, 112 Si layer 104, 114 SiO ₂ layer 122, 130 Opening

Claims (10)

A cantilever type sensor for detecting a measurement object contained in a liquid,
A cantilever having at least one end fixed to the support and having a flow path formed therein;
A piezoelectric element composed of a piezoelectric body and electrode portions formed on both sides of the piezoelectric body, and disposed on at least one surface of the cantilever;
A drive unit that applies a voltage to the electrode unit of the piezoelectric element to vibrate the cantilever;
A detection unit for detecting vibration of the cantilever from expansion and contraction of the piezoelectric element;
A cantilever type sensor having a liquid supply means for flowing a liquid through the flow path of the cantilever.   The cantilever type sensor according to claim 1, wherein the piezoelectric body is a composition of perovskite crystal containing Pb.   The cantilever type sensor according to claim 1, wherein the piezoelectric body is a composition of perovskite crystal not containing Pb.   The cantilever type sensor according to any one of claims 1 to 3, wherein only one end of the cantilever is fixed to the support portion.   The cantilever sensor according to claim 1, wherein both ends of the cantilever are fixed to a support portion. A cantilever type sensor according to any one of claims 1 to 5,
A frequency calculation unit for calculating a resonance frequency of the cantilever from a value detected by the detection unit;
The resonance frequency calculated by the calculation unit is compared with the resonance frequency of the cantilever when a liquid that does not contain the measurement object flows through the flow path, and the measurement object in the flow path is detected from the comparison result. The substance detection system which has a detection part to perform.   The said detection part is a substance detection system of Claim 6 which detects the mass of the said measuring object from the said comparison result.   The substance detection system according to claim 6, wherein the detection unit detects the presence or absence of the substance to be measured from the comparison result. A substance detection method for detecting a measurement target in a liquid,
A liquid is allowed to flow through the channel of the cantilever in which a piezoelectric element is disposed on at least one surface and a channel is formed inside;
A voltage is applied to the piezoelectric element, and the piezoelectric element is expanded and contracted to vibrate the cantilever in a state where the liquid is flowed,
Detecting the vibration of the cantilever with the piezoelectric element;
Detecting the resonance frequency of the cantilever in the state in which the liquid is flowed from the detected vibration;
Comparing the detected resonance frequency with the resonance frequency of the cantilever in a state where a liquid that does not contain the measurement target is passed through the flow path,
A substance detection method that detects the measurement target from the comparison result.   The substance detection method according to claim 9, wherein the mass of the measurement target is detected from the comparison result.

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